초록 ▼

The present application relates to microfluidic devices and related technologies, and to chemical processes using such devices. More specifically, the application discloses a fully automated synthesis of radioactive compounds for imaging, such as by positron emission tomography (PET), in a fast, eff

The present application relates to microfluidic devices and related technologies, and to chemical processes using such devices. More specifically, the application discloses a fully automated synthesis of radioactive compounds for imaging, such as by positron emission tomography (PET), in a fast, efficient and compact manner. In particular, this application describe an automated, stand-alone, microfluidic instrument for the multi-step chemical synthesis of radiopharmaceuticals, such as probes for PET and a method of using such instruments.

대표청구항 ▼

What is claimed: 1. A microfluidic system for synthesis of a radiolabeled compound, the system configured to transfer and facilitate the reaction of microliters and/or nanoliters of reagent, the system comprising: a microfluidic synthesis chip configured for conducting batch reactions, the chip com

What is claimed: 1. A microfluidic system for synthesis of a radiolabeled compound, the system configured to transfer and facilitate the reaction of microliters and/or nanoliters of reagent, the system comprising: a microfluidic synthesis chip configured for conducting batch reactions, the chip comprising; a reaction chamber; an inlet flow channel in communication with the reaction chamber and configured to pass reagent into the reaction chamber, the inlet flow channel having a valve configured to regulate flow to the reaction chamber; and a plurality of outlet channels in communication with the reaction chamber and configured to pass reagent out of the reaction chamber, each channel having a valve configured to close to trap reagent within the reaction chamber during a reaction and release reagent and products when the reaction is complete; and a reagent source comprising at least one reagent, the reagent source in fluid communication with the reaction chamber via the at least one flow channel, wherein the reaction chamber has an area substantially greater than a cross-sectional area of each of the inlet flow channel and the outlet channels. 2. The system of claim 1, further comprising a purification system in fluid communication with the synthesis chip, a product receptacle in fluid communication with said purification system, and radiation shielding substantially enclosing one or more of: a) the reagent source b) microfluidic chip; c) the purification system; and d) the product receptacle. 3. The system of claim 1, wherein said system does not require a separate hot cell. 4. The system of claim 1, further comprising a temperature control system operatively coupled to the microfluidic chip, the temperature control system comprising a heat-exchanger. 5. The system of claim 1, wherein said inlet flow channel valves and outlet flow channel valves are selected from the group consisting of a check valve and a 3-way valve. 6. The system of claim 1, further comprising a gas source in communication with the reagent source such that, the system is pressurized by gas from said inlet and the speed with which said reagents are conveyed from said source to said reaction chamber is controlled by pressure of gas. 7. The system of claim 6, further comprising a gas permeable membrane adjacent the reaction chamber and wherein the speed with which said reagents are conveyed from said reagent source to said reaction chamber is controlled by the thickness and/or composition of said membrane. 8. The system of claim 2, further comprising a vacuum in communication with the reaction chamber, wherein the radiation shield substantially encloses the vacuum. 9. A portable microfluidic system for synthesis of a radiolabeled compound, the system configured to transfer and facilitate the reaction of microliters and/or nanoliters of reagent, the system comprising: a microfluidic synthesis chip configured to conduct batch reactions comprising: a reaction chamber; a vent in communication with the reaction chamber; at least one flow channel in communication with the reaction chamber; at least one valve configured to regulate flow to or from the reaction chamber; and a reagent source comprising at least one reagent in fluid communication with the reaction chamber via the flow channel; and a filter in communication with the reaction chamber and an area outside of the system, the filter configured to filter exhaust from the reaction chamber wherein the valve is configured to close to trap reagent within the reaction chamber during a reaction during a reaction and release reagent and products when the reaction is complete. 10. The system of claim 1, wherein the inlet and outlet channels have a cross-section of no more than about 300 μm. 11. The system of claim 1, wherein the reagent source contains about 5 μL to about 50 μL of reagent. 12. The system of claim 1, wherein the reaction chamber has a diameter and a height, wherein the diameter is about 1,000 μm to about 20,000 μm and the diameter to height ratio is about 3 to about 10. 13. The system of claim 9, further comprising a gas source in communication with the at least one reagent such that gas conveys the at least one reagent to the reaction chamber. 14. The system of claim 13, wherein the microfluidic chip further comprises a gas permeable membrane in communication with the reaction chamber. 15. The system of claim 14, wherein the vent is in communication with the gas permeable membrane. 16. The system of claim 9, further comprising a vacuum in communication with the reaction chamber and the filter. 17. The system of claim 9, further comprising a radiation shield substantially enclosing the microfluidic chip and the filter. 18. The system of claim 16, further comprising a radiation shield substantially enclosing the microfluidic chip, the filter and the vacuum. 19. The system of claim 9, wherein the flow channel has a cross-section of no more than about 300 μm. 20. The system of claim 19, wherein the reagent source contains about 5 μL to about 1000 μL of reagent. 21. The system of claim 19, wherein the reagent source contains about 5 μL to about 15 μL of reagent. 22. The system of claim 19, wherein the reaction chamber has a diameter and a height, wherein the diameter is about 1,000 μm to about 20,000 μm and the diameter to height ratio is about 3 to about 10. 23. The system of claim 15, wherein the gas-permeable membrane is positioned between the reaction chamber and the vent. 24. The system of claim 23, wherein the vent is about 250 μm wide and about 1000 mm deep. 25. The system of claim 18, wherein filter is in communication with an area outside of the radiation shield via the vacuum. 26. The system of claim 9, further comprising a trap chip or cartridge upstream of and in communication with the microfluidic chip. 27. The system of claim 26, wherein the reagent source comprises a plurality of reagent sources, one reagent source comprising 18F—H2O and one reagent source comprising K2CO3 upstream of the trap chip or cartridge. 28. The system of claim 13, further comprising: a temperature control system operatively coupled to the microfluidic chip, the temperature control system comprising a heat exchanger; a pressure control system operatively coupled to the microfluidic chip, the pressure control system comprising a vacuum; a controller operatively coupled to and controlling the function of at least one component selected from the group consisting of the gas delivery source, the vacuum system, the temperature control system and the valve on the synthesis chip; and at least one external input device coupled to the controller. 29. The system of claim 27, wherein one reagent source comprises MeCN, one reagent source comprises mannose triflate, one reagent source comprises K222, one reagent source comprises HCl and one reagent source comprises H2O, wherein each reagent source is upstream of the microfluidic chip. 30. The system of claim 9, further comprising at least one controller operatively coupled to and controlling the function of at least one component selected from the group consisting of the gas delivery source, the reagent source and the microfluidic chip valve. 31. A microfluidic system for synthesis of a radiolabeled compound, the system configured to transfer and facilitate the reaction of microliters and/or nanoliters of reagent, the system comprising: a microfluidic synthesis chip configured to conduct batch reactions, the microfluidic synthesis chip comprising: a substrate comprising: a reaction chamber; an inlet channel in communication with the reaction chamber and configured to pass reagent into the reaction chamber, the inlet channel comprising a valve configured to regulate flow to the reaction chamber; an outlet channel in communication with the reaction chamber and configured to pass reagent out of the reaction chamber, the outlet channel having a valve configured to control reagent and product flow out of the reaction chamber; a gas permeable membrane in communication with the reaction chamber; a vent in communication with the reaction chamber; a reagent source in fluid communication with the reaction chamber via the inlet channel; and a gas source in communication with the at least one reagent such that gas conveys the reagent to the reaction chamber, wherein the valve of the outlet channel is configured to close to trap reagent within the reaction chamber during a reaction and release reagent and products when the reaction is complete. 32. The system of claim 31, wherein the reaction chamber has a diameter and a depth, the diameter substantially larger than the depth. 33. The system of claim 31, wherein the gas permeable membrane is positioned between the reaction chamber and the vent and wherein the gas permeable membrane is in communication with the vent. 34. The system of claim 31, wherein the channel has a cross-section no greater than about 300 μm. 35. The system of claim 31, wherein the reagent source contains no more than about 1000 μL of reagent. 36. The system of claim 32, wherein the diameter of the reaction chamber is about 1,000 μm to about 20,000 μm and the diameter to height ratio is about 3 to about 10. 37. The system of claim 36, wherein the height of the reaction chamber is about 250 μm. 38. The system of claim 31, wherein the gas-permeable membrane defines a portion of the reaction chamber. 39. The system of claim 31, wherein the microfluidic chip further comprises a plurality of outlet channels in communication with the reaction chamber, each channel configured to pass reagents and products out of the reaction chamber, each channel having a valve configured to trap reagent within the reaction chamber during a reaction and release reagent and products when the reaction is complete. 40. The system of claim 26, wherein the trap chip or cartridge comprises an ion-exchange column having a resin of about 1 μL to about 3 μL, 41. The system of claim 26, wherein the trap chip or cartridge comprises an ion-exchange column having a resin with about 8% cross-linking. 42. The system of claim 41, wherein the resin has a dry mesh size of about 50 to about 400. 43. The system of claim 9, wherein the reagent source comprises microliters or nanoliters of liquid. 44. The system of claim 9, wherein the reaction chamber has a rounded wall. 45. The system of claim 31, wherein the reaction chamber has a rounded wall.